Endothelium-derived relaxing, contracting and hyperpolarizing factors of mesenteric arteries of hypertensive and normotensive rats

1 Differences in the acetylcholine (ACh)-induced endothelium-dependent rela xation and hyperpolarization of the mesenteric arteries of Wistar Kyoto rat s (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were studi ed. 2 Relaxation was impaired in preparations from SHRSP and tendency to revers e the relaxation was observed at high concentrations of ACh in these prepar ations. 3 Relaxation was partly blocked by N-G-nitro-L-arginine (L-NOARG, 100 mu M) and, in the presence of L-NOARG, tendency to reverse the relaxation was ob served in response to higher concentrations of ACh, even in preparations fr om WKY. The relaxation remaining in the presence of L-NOARG was also smalle r in preparations from SHRSP. 4 The tendency to reverse the relaxation observed at higher concentrations of ACh in preparations from SHRSP or WKY in the presence of L-NOARG were ab olished by indomethacin (10 mu M). 5 Elevating the K+ concentration of the incubation medium decreased relaxat ion in the presence of both indomethacin and L-NOARG. 6 Relaxation in the presence of L-NOARG and indomethacin was reduced by the application of both apamin (5 mu M) and charybdotoxin (0.1 mu M). This sug gests that the relaxation induced by ACh is brought about by both endotheli um-derived relaxing factor (EDRF, nitric oxide (NO)) and hyperpolarizing fa ctor (EDHF), which activates Ca2+-sensitive K+ channels. 7 Electrophysiological measurement revealed that ACh induced endothelium-de pendent hyperpolarization of the smooth muscle of both preparations in the presence of L-NOARG and indomethacin; the hyperpolarization being smaller i n the preparation from SHRSP than that from WKY. 8 These results suggest that the release of both NO and EDHF is reduced in preparations from SHRSP. In addition, indomethacin-sensitive endothelium-de rived contracting factor (EDCF) is released from both preparations; the rel ease being increased in preparations from SHRSP.